Reconstruction of a replication-competent ancestral murine endogenous retrovirus-L.
Reconstruction of a replication-competent ancestral murine endogenous retrovirus-L.
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DOI：
10.1186/s12977-018-0416-3
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发表时间：
2018-05-02
期刊：
影响因子：
3.3
通讯作者：
Bieniasz PD
中科院分区：
文献类型：
--
作者：
Blanco-Melo D;Gifford RJ;Bieniasz PD
大约10%的小鼠基因组由内源性逆转录病毒（ERV）组成，这些病毒代表了过去逆转录病毒感染的分子化石记录。一种这样的逆转录病毒，鼠ERV-L（MuERV-L）是一种env缺陷型ERV，其经历了间歇性增殖，最近的扩增发生在约200万年前。MuERV-L相关序列已被小鼠用于抗逆转录病毒防御，并可能作为某些基因的启动子，调节早期小鼠胚胎的全能性。然而，尚未观察到现代小鼠基因组中存在的MuERV-L序列进行复制。在这里，我们描述了重建的祖先MuERV-L（ancML）序列通过古病毒学分析MuERV-L元素在现代小鼠基因组。合成得到的MuERV-L（ancML）序列并嵌入报告基因。重建的MuERV-L（ancML）可以复制的方式，是依赖于逆转录和从头产生的整合。值得注意的是，MuERV-L（ancML）表现出窄的宿主范围。干扰素-α可抑制MuERV-L（ancML）的复制，提示存在干扰素诱导的基因可抑制MuERV-L的复制。虽然小鼠APOBEC 3能够限制MuERV-L（ancML）的复制，但对内源性MuERV-L序列的检查表明，APOBEC 3介导的超突变对MuERV-L的影响极小。祖先MuERV-L序列的重建突出了逆转录病毒化石记录照亮古代事件的潜力，并使逆转录病毒元素对动物进化的影响研究成为可能。本文的在线版本（10.1186/s12977-018-0416-3）包含补充材料，可供授权用户使用。
About 10% of the mouse genome is composed of endogenous retroviruses (ERVs) that represent a molecular fossil record of past retroviral infections. One such retrovirus, murine ERV-L (MuERV-L) is an env-deficient ERV that has undergone episodic proliferation, with the most recent amplification occurring ~ 2 million years ago. MuERV-L related sequences have been co-opted by mice for antiretroviral defense, and possibly as promoters for some genes that regulate totipotency in early mouse embryos. However, MuERV-L sequences present in modern mouse genomes have not been observed to replicate. Here, we describe the reconstruction of an ancestral MuERV-L (ancML) sequence through paleovirological analyses of MuERV-L elements in the modern mouse genome. The resulting MuERV-L (ancML) sequence was synthesized and a reporter gene embedded. The reconstructed MuERV-L (ancML) could replicate in a manner that is dependent on reverse transcription and generated de novo integrants. Notably, MuERV-L (ancML) exhibited a narrow host range. Interferon-α could reduce MuERV-L (ancML) replication, suggesting the existence of interferon-inducible genes that could inhibit MuERV-L replication. While mouse APOBEC3 was able to restrict the replication of MuERV-L (ancML), inspection of endogenous MuERV-L sequences suggested that the impact of APOBEC3 mediated hypermutation on MuERV-L has been minimal. The reconstruction of an ancestral MuERV-L sequence highlights the potential for the retroviral fossil record to illuminate ancient events and enable studies of the impact of retroviral elements on animal evolution. The online version of this article (10.1186/s12977-018-0416-3) contains supplementary material, which is available to authorized users.
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DOI：
10.3390/v6124926
发表时间：
2014-12-09
期刊：
Viruses
影响因子：
--
作者：
Armezzani A;Varela M;Spencer TE;Palmarini M;Arnaud F
通讯作者：
Arnaud F
DOI：
10.1111/j.1742-4658.2009.06909.x
发表时间：
2009-03
期刊：
The FEBS journal
影响因子：
--
作者：
Champoux JJ;Schultz SJ
通讯作者：
Schultz SJ
影响因子：
6.7
作者：
Perez-Caballero D;Soll SJ;Bieniasz PD
通讯作者：
Bieniasz PD
影响因子：
64.8
作者：
Best, S;LeTissier, P;Stoye, JP
通讯作者：
Stoye, JP
影响因子：
14.9
作者：
Hubbard, T;Barker, D;Clamp, M
通讯作者：
Clamp, M